These projects have addressed the signal transduction mechanisms of the lymphohematopoietic cytokines IL 2, IL 3, GM-CSF and Epo. Though none of the receptors for these factors encodes a protein kinase, stimulation of appropriate target cells results in increases in phosphorylation of a common subset of proteins on either tyrosine or serine residues. To better understand signal transduction mechanisms important in the proliferative response, we have characterized both a tyrosine and serine kinase substrate representing points of convergence in the signal transduction pathway of IL 2, IL 3, GM-CSF and Epo. We have found a highly conserved serine kinase substrate to be the actin binding protein 1-plastin. The factor-induced phosphotyrosylprotein has several characteristics consistent with those of a tyrosine kinase. Further, this tyrosine kinase can be found in association with the Epo receptor and is constitutively phosphorylated in cells rendered Epo-independent through either transformation with Friends spleen focus forming virus (SFFV) or transfected with gp55, the envelope glycoprotein of the SFFV. In addition, our work also suggests that this protein may be associated with other cytokine receptors and may represent a protein tyrosine kinase critical for signal transduction of a number of cytokines.